TY - JOUR T1 - The physiological disposition of lovastatin. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 166 LP - 173 VL - 17 IS - 2 AU - D E Duggan AU - I W Chen AU - W F Bayne AU - R A Halpin AU - C A Duncan AU - M S Schwartz AU - R J Stubbs AU - S Vickers Y1 - 1989/03/01 UR - http://dmd.aspetjournals.org/content/17/2/166.abstract N2 - Lovastatin is a pro-drug lactone whose open chain beta-hydroxy-acid (HA) is a potent inhibitor of hydroxymethylglutaryl-CoA-reductase and thus of cholesterol synthesis. Because the liver is the major site of cholesterolgenesis, it is the principal target organ for agents of this class. In animals, lovastatin is not as well absorbed as HA given per se, but that fraction that is absorbed reaches the portal circulation largely unchanged and is more efficiently extracted by the liver, after which it is reversibly biotransformed to HA and irreversibly to other enzymatically active products. These, like HA, maintain high hepatic gradients relative to all tissues examined. The minimal systemic burden for HA is attributable in part to the metabolic equilibrium, lovastatin in equilibrium HA, the opposing reactions for which appear to be present in most tissues. Excretion is very largely biliary in all species. Detailed comparisons of absorption, distribution, metabolism, and excretion profiles presented here and elsewhere indicate dogs to be the most appropriate paradigm for humans for study of lovastatin disposition. ER -